Major complications after intraoperative radiotherapy with low-energy x-rays in early breast cancer.

PURPOSE: To describe and analyze major local complications after intraoperative radiotherapy (IORT) with low-energy x­rays during breast-conserving surgery (BCS) in early breast cancer. METHODS: Ten women out of 408 who were treated with IORT between 2002 and 2017 and subsequently developed a severe local complication requiring surgical intervention were retrospectively identified and analyzed. Demographic, clinical, and surgical parameters as well as complication characteristics and treatment methods were evaluated. RESULTS: At initial presentation, eight patients (80%) showed redness, six (60%) seroma, six (60%) wound infection, six (60%) suture dehiscence, and four (40%) induration of the former surgical area. Hematoma and necrosis were observed in one case (10%) each. Time interval until appearance of the first symptoms ranged from directly postoperative until 15 years postoperatively (median 3.1 months). Initial treatment modalities comprised antibiotic therapy (n = 8/80%) and transcutaneous aspiration of seroma (n = 3/30%). In the majority of patients, smaller surgical interventions (excision of a necrotic area/fistula [n = 6/60%] or secondary suture [n = 5/50%]) were sufficient to overcome the complication, yet larger interventions such as complex flap surgery and mastectomy were necessary in one patient each. CONCLUSION: IORT is an efficient and safe treatment method as < 2.5% of all IORT patients experienced major local complications. However, it seems to pose the risk of causing severe local complications that may require lengthy and burdensome treatment. Thorough preoperative counseling, implementation of recommended intraoperative precautions, and high vigilance for first symptoms of complications during follow-up appointments are necessary measures.

Intraoperative radiotherapy (IORT) of early breast cancer with low-energy x-rays in breast-conserving surgery : Prospective identification of pre- and intraoperative factors influencing the feasibility of IORT.

PURPOSE: The aim of this study is to identify pre- and intraoperative factors indicating the feasibility of intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS). MATERIALS AND METHODS: From January 2018 to December 2019, a total of 128 women undergoing BCS due to early breast cancer were included in this prospective observational study, independent of whether IORT was planned or not. Patient and tumor characteristics as well as surgical parameters that could potentially influence the feasibility of IORT were recorded for the entire collective. In addition, a preoperative senological assessment was performed and analyzed to assess the feasibility of IORT. Logistic regression was then used to identify relevant preoperative parameters and to generate a formula predicting the feasibility of IORT. RESULTS: Of the 128 included women undergoing BCS, 46 were preoperatively rated to be feasible, 20 to be questionably feasible for IORT. Ultimately, IORT was realized in 30 patients. The most frequent reasons for omission of IORT were insufficient tumor-to-skin distance and/or an excessively large tumor cavity. Small clinical tumor size and large tumor-to-skin distance according to preoperative ultrasound were significantly related to accomplishment of IORT. CONCLUSION: We observed that preoperative ultrasound-based tumor-skin distance is a significant factor in addition to already known parameters to predict feasibility of IORT. Based on our findings we developed a formula to optimize IORT planning which might serve as an additional tool to improve patient selection for IORT in early breast cancer.

The effectiveness of integrated online health-coaching on physical activity and excessive gestational weight gain: a prospective randomized-controlled trial.

PURPOSE: Low levels of physical activity during pregnancy go along with increased risks for numerous health complications. We investigated whether an integrated lifestyle intervention leads to higher levels of physical activity and reduces the rate of excessive gestational weight gain (EGWG). METHODS: We conducted a randomized-controlled trial on 97 pregnant women, randomly assigned to receive an additional telehealth lifestyle intervention (experimental group, EG; n = 49) or conventional antenatal care (control group, CG; n = 48). The core lifestyle intervention comprised regular video calls, providing integrated personal support and motivation to physical activity. The primary outcome was change in physical activity measured in steps per day. An additional exploratory outcome was the proportion of participants with EGWG. RESULTS: The mean step count during the third trimester was 6483 steps/day (EG) and 5957 steps/day (CG), respectively (p = 0.078). Repeated-measures ANOVA revealed a significant interaction effect (p = 0.045) reflecting an overall increase of 497 steps per day in the EG vs. a decrease of 300 steps per day in the CG. The proportion of participants who met the IOM recommendation for total weight gain during pregnancy was significantly higher in the EG (p = 0.048) and the ratio of women that gained excessively was higher in the CG (p = 0.026). CONCLUSIONS: We assume that the personalized online intervention supports women in increasing or at least maintaining their level of physical activity during the course of pregnancy. Additionally, it reduces the rate of excessive weight gain.

Relationship of Ki-67 index in biopsies of metastatic breast cancer tissue and circulating tumor cells (CTCs) at the time of biopsy collection.

BACKGROUND: The proliferation marker Ki-67 is a major pathological feature for the description of the state of disease in breast cancer. It helps to define the molecular subtype and to stratify between therapy regimens in early breast cancer and helps to assess the therapy response. Circulating tumor cells (CTCs) are a negative prognostic biomarker for progression free (PFS) and overall survival (OS) in patients with metastatic breast cancer. Therefore, the CTC count is often described as surrogate for the tumor burden. Both, decrease of Ki-67 and CTC count are considered as evidence for therapy response. The presented work analyzed the correlation between the Ki-67 indices of metastatic tissue biopsies and CTC counts in biopsy time-adjacent peripheral blood samples. PATIENTS AND METHODS: Blood samples from 70 metastatic breast cancer patients were obtained before the start of a new line of systemic therapy. CTCs were enumerated using CellSearch® (Menarini Silicon Biosystems, Bologna, Italy) whereas intact CTCs (iCTCs) and non-intact or apoptotic CTCs (aCTCs) were distinguished using morphologic criteria. The proportion of cells expressing Ki-67 was evaluated using immunohistochemistry on biopsies of metastases obtained concurrently with CTC sampling before the start of a new line of systemic therapy. RESULTS: 65.7% of patients had a Ki-67 index of > 25%. 28.6% of patients had ≥ 5, 47.1% ≥ 1 iCTCs. 37.1% had ≥ 5, 51.4% ≥ 1 aCTCs. No correlation was shown between Ki-67 index and iCTC and aCTC count (r = 0.05 resp. r = 0.05, Spearman's correlation index). High CTC-counts did not coincide with high Ki-67 index. High Ki-67, ≥ 5 iCTCs and aCTCs are associated with poor progression free (PFS) and overall survival (OS). CONCLUSION: CTCs and Ki-67 are independent prognostic markers in metastatic breast cancer. High Ki-67 in metastatic tumor tissue is not correlated to high iCTC or aCTC counts in peripheral blood.

Prevalence of higher-grade dysplasia in persistently high-risk human papillomavirus positive, cytology negative women after introduction of the new cervical cancer screening in Germany.

PURPOSE: According to the recently implemented organized cervical cancer screening program in Germany, women older than 35 years with negative cytology but persistent high-risk human papilloma virus (hrHPV) infection > 12 months should be referred to colposcopy for further evaluation. This study aimed to present and dissect colposcopic and histopathological findings with particular focus on associated hrHPV genotypes. METHODS: This study is a retrospective analysis of clinical data from 89 hrHPV positive patients with normal cytology who underwent colposcopic examination at a certified dysplasia outpatient clinic in Germany in 2021. RESULTS: While 38 (43%) women had a normal colposcopic finding, 45 (51%) had minor and 6 (7%) major changes. Thirty-one (35%) of the women were HPV 16 and/or HPV 18 positive and 58 (65%) women were positive for other hrHPV only. Among patients who underwent colposcopy with biopsies (in case of an abnormal finding or type 3 transformation zone, n = 68), eight (12%) had cervical intraepithelial neoplasia (CIN) 3 and six (9%) had CIN 2. The proportion of women diagnosed with CIN 3 varied among different hrHPV genotypes (HPV 16: 11%, HPV 18: 33%, HPV 31: 27%, HPV 33: 33%, HPV 52: 33%). CONCLUSION: Persistently hrHPV positive women with negative cytology are at increased risk of being diagnosed with CIN 3. As CIN 3 prevalence seems to differ with regard to hrHPV strain, immediate HPV genotyping for risk stratification and subsequent early referral for colposcopy might constitute a feasible strategy.

The hysterectomy: influence of the surgical method in benign disease on convalescence and quality of life.

PURPOSE: The aim of this study was to evaluate the postoperative course after different methods of hysterectomy for benign diseases with special emphasis on time to recovery and patient-centred aspects such as postoperative quality of life and satisfaction. METHODS: A collective of 242 women who had undergone vaginal hysterectomy (VH), laparoscopic supracervical hysterectomy (LASH) or total laparoscopic hysterectomy (TLH) for various benign conditions was studied in this retrospective investigation. Patients completed a standardised questionnaire addressing quality of life, recovery and sick leave as well as general questions on their postoperative course after hysterectomy. RESULTS: A total of 242 cases were analysed (82 VH, 92 LASH and 68 TLH). The data demonstrate significant differences in regard to age between groups. The present study shows shorter hospitalisation with laparoscopy, with LASH patients returning to work at least one week earlier on average. There were no relevant differences in the overall postoperative course during the index hospital stay. In the long run, laparoscopic patients were not more satisfied with their choice than VH patients. CONCLUSION: No significant long-term differences could be observed in terms of quality of life and overall postoperative satisfaction between VH and LH groups. In regard to socioeconomic aspects, laparoscopic approaches were associated with shorter hospitalisation and LASH patients returning to work at least one week earlier on average. Contrary to these data on objective recovery; however, a laparoscopic approach did not lead to patient-perceived, i.e. subjective improvement of time to full recovery.

First experiences with a diode laser in major gynecological laparoscopic procedures show lack of benefit and impaired feasibility.

PURPOSE: The aim of this study is to evaluate feasibility and potential benefit of a diode laser in major laparoscopic procedures in gynecology. METHODS: Between 2018 and 2020, a total of 42 cases were enrolled in this study comparing standard electrosurgery with diode laser-supported therapy in laparoscopic supracervical hysterectomy (LASH), total laparoscopic hysterectomy (TLH), or laparoscopic myoma enucleation (LME). Dual wavelength 45 W diode laser light was used to cut and coagulate during laparoscopy in the prospective interventional arm consisting of 11 cases, while 31 matching patients who received conventional treatment with monopolar/bipolar current for the same interventions were retrospectively identified in our laparoscopy database. Recruitment in the prospective interventional laser diode arm was terminated after only 11 patients (instead of planned 50) due to intense hemorrhage and massive smoke development. RESULTS: A total of 42 cases were analyzed (11 LME, 19 LASH, and 12 TLH). Strong smoke development was evident in all 11 cases in the diode laser arm. It was necessary to convert to bipolar or monopolar current in all hysterectomies (n = 9) with initial diode laser implementation due to increased bleeding and smoke development. Conventional current sources had to be used in LMEs (n = 2) due to excessive bleeding and poor visibility during enucleation of the fibroid. A significant difference (p < 0.0001) was observed regarding smoke development when comparing the laser arm with the control arm. CONCLUSION: We found a 45-W diode laser to be inferior to electrosurgical techniques for major laparoscopic gynecologic surgeries regarding bleeding control and smoke development.

[Follow-up Routine in Primary Care of Women after Hypertensive Disorders in Pregnancy - a Single-Center, Survey-Based Study]. / Versorgungsrealität von Frauen nach hypertensiver Schwangerschaftserkrankung ­ eine monozentrische fragebogenbasierte Analyse.

INTRODUCTION: Women with a history of a hypertensive disorders of pregnancy have a significantly higher risk of future cardiovascular diseases and are therefore recommended to participate in screening examinations and counseling on primary prevention. To understand the current routine of postpartum care, we examined how many women engage in follow-up examinations and whether counseling takes place. METHODOLOGY: Single-center, survey-based study of 113 women affected by hypertensive disorders of pregnancy between 2014 and 2019. Descriptive analysis was used to analyze the responses. RESULTS: A total of 54% of the women engaged in follow-up. Of the participants, 47% were informed about their diagnosis in a personal conversation and possible consequences were pointed out. Of the 67 women with a BMI≥25 kg/m2, 23% received a recommendation to increase physical activity, and 13% of these women were advised to reduce their weight. Significantly more women with a higher burden of disease (BMI, p=0.027; arterial hypertension, p=0.016) and a severe form of hypertensive pregnancy disorder (eclampsia, intensive care treatment, each p=0.016) engaged in follow-up care. CONCLUSIONS: The present results suggest that the strategies to prevent cardiovascular diseases and detect cardiovascular risk factors have not been consistently pursued. After a hypertensive disorder of pregnancy, every woman should receive a recommendation to engage in follow-up examinations.

New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer.

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Cardiac serum marker alterations after intraoperative radiotherapy with low-energy x-rays in early breast cancer as an indicator of possible cardiac toxicity.

PURPOSE: To assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x­rays for early breast cancer. METHODS: We prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x­rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated. RESULTS: There were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N­terminal fragment of B­type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279). CONCLUSION: Troponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.

Female genital injury-which findings have to be considered physiological using colposcopy with and without toluidine blue dye?

This study aimed to assess the validity and efficacy of blue dye in colposcopic assessment of genital injury in pre- and postmenopausal women with and without history of consensual sexual intercourse. Two hundred women were prospectively enrolled and examined colposcopically with and without toluidine blue dye in order to detect and categorize genital lesions (laceration, bruise and abrasion). Examination of genital trauma was accomplished in a standardized way and findings were photo documented. A wide range of influencing factors with a potential impact on prevalence and nature of genital injury was recorded beforehand using a questionnaire. The frequency of diagnostic injury differed substantially depending on the examination technique, ranging from 9% using colposcopic magnification only to 28% with the additional use of toluidine blue dye. A vertical laceration affecting the posterior fourchette was the most frequent lesion detected (17%, n = 32). Menopausal status seems to have significant impact on genital injury prevalence (p = 0.0165), as 42% (16/ 38) of postmenopausal compared to 24% (36/ 151) of premenopausal women had at least one genital lesion. Furthermore, vaginal medication (p = 0.0369), vaginal dryness (p = 0.0228), dyspareunia (p = 0.0234) and low frequency of sexual intercourse (p = 0.0022) were found to significantly correlate with the presence of genital lesions. According to our findings, standardized colposcopy in combination with toluidine blue dye facilitates accurate assessment of genital lesions. Genital trauma situated at another site than the posterior part of the vaginal introitus seems to be uncommon after consensual intercourse.

Intraoperative radiotherapy for breast cancer treatment efficiently targets the tumor bed preventing breast adipose stromal cell outgrowth.

OBJECTIVES: Mesenchymal stromal cells (MSC) in bone marrow have been shown to be radioresistant, which is related to pronounced DNA repair mechanisms. Intraoperative radiotherapy (IORT) during breast-conserving surgery for early breast cancer is an innovative technique applying low energy x­ray to the tumor bed immediately after removal of the tumor. IORT is considered to reduce the risk of local tumor recurrence by directly targeting cells of the tumor bed and altering the local microenvironment. Aim of this study was to investigate whether IORT affects the outgrowth potential of breast adipose tissue-derived MSC (bASC) as part of the tumor bed. MATERIALS AND METHODS: After surgical tumor resection, biopsies of the tumor bed were taken before (pre IORT) and after IORT (post IORT) and processed applying well-established protocols for ASC isolation and characterization. RESULTS: In all, 95% of pre IORT tumor bed samples yielded persistently outgrowing bASC with typical ASC characteristics: fibroblastoid morphology, proliferation, adipogenic and osteogenic differentiation and ASC surface marker expression. However, none of the post IORT samples yielded persistent outgrowth of bASC. CONCLUSIONS: After breast-conserving surgery, approximately 90% of local recurrences emerge in close proximity to the initial tumor bed, potentially reflecting a significant contribution of the tumor bed to relapse. Our data show that IORT, besides the proven effect on breast cancer cells, efficiently modifies the tumor environment by having an impact on tumor bed bASC. This effect on tumor bed stromal cells might contribute to reduce the risk of tumor relapse and metastases.

Long-term outcome after intraoperative radiotherapy as a boost in breast cancer.

PURPOSE: To investigate long-term oncological outcome and incidence of chronic side effects in patients with breast cancer and intraoperative radiotherapy given as an upfront boost (IORT boost). METHODS: Retrospective analysis of 400 patients with an IORT boost with low-energy X­rays (20 Gy), subsequent whole-breast irradiation (46-50 Gy), and annual oncological follow-up. Side effects were prospectively evaluated (LENT-SOMA scales) over a period of up to 15 years. Side effects scored ≥grade 2 at least three times during follow-up were judged to be chronic. RESULTS: The median age was 63 years (30-85) and the median follow-up was 78 months (2-180) after IORT boost. In 15 patients a local recurrence occurred, resulting in a local recurrence rate at 5, 10, and 15 years of 2.0%, 6.6%, and 10.1%, respectively. The overall survival rates at 5, 10, and 15 years were 92.1%, 81.8%, and 80.7%, respectively. The most common high-grade side effects were fibrosis (21%) and pain (8.6%). The majority of side effects occurred within the first 3 years. The actuarial rates of chronic fibrosis were 19.1% and 21.1% at 5 and ≥8 years, of chronic pain 8.6% at ≥4 years, of chronic edema of the breast 2.4% at ≥2 years, of chronic lymphedema 0.0% at 5 and 10 years, and of chronic hyperpigmentation 0.5% at ≥2 years. Side effects were similar or less than expected from an external beam boost. CONCLUSION: IORT boost appears to be a highly efficient and safe method for upfront delivery of the tumor bed boost in high-risk breast cancer patients.

Influence of Peripartum Expectations, Mode of Delivery, and Perineal Injury on Women's Postpartum Sexuality.

BACKGROUND: Sexual health has been identified as an important factor for postpartum quality of life. Although pregnancy-related changes in anatomy and metabolism return to their prepregnancy state, female sexual function may not be at the level it was before birth because of physical and psychological changes. AIM: The goal of our study was to explore the influence of the mode of delivery, perineal injury, and peripartum expectations on postpartum sexual function. METHODS: Between 2013 and 2018, 522 women were enrolled in this prospective investigation. At time of recruitment during the peripartum hospitalization, patients completed a standardized questionnaire addressing expectations concerning postpartum sexuality with focus on expected influence of the mode of delivery. Sexual function was evaluated using the Female Sexual Function Index (FSFI) and Sexual Activity Questionnaire (SAQ) at time of recruitment to evaluate baseline sexual function (4 weeks before pregnancy). Follow-up assessments were conducted at 3, 6, and 12 months postpartum. OUTCOMES: Peripartum expectations, influence of the mode of delivery, and perineal injury were analyzed for their impact on women's sexual function within 12 months postpartum by repetitive FSFI and SAQ assessments. RESULTS: A total of 522 women with 263 spontaneous vaginal deliveries, 41 operative vaginal deliveries, and 218 cesarean sections were analyzed. Although the data demonstrate a significant postpartum decline in sexual function at 3 and 6 months postpartum, sexual functioning converges to baseline prepregnancy values 12 months postpartum. This observation was independent of the mode of delivery and perineal injuries with no significant between-group differences at any of the analyzed time points. Apart from breastfeeding, for which negative anticipations resulted in impaired sexuality, women's expectations (pertaining to quantity and quality of female orgasm, partner's sexuality, fear of altered sexuality, frequency of intercourse, the mode of delivery) do not influence female sexual function at 12 months postpartum. CLINICAL IMPLICATIONS: Deciphering the potential influence of patient expectations as well as pregnancy- and childbirth-related aspects on female postpartum sexuality will help in the effort to improve women's postpartum sexual health. STRENGTHS & LIMITATIONS: As a strength of this study, postpartum sexuality was independently assessed with 2 different scoring systems (FSFI and SAQ). Limitations include that our follow-up is incomplete and amounts to about 2-thirds of patients who were initially recruited. CONCLUSION: The mode of delivery and perineal trauma do not influence women's postpartum sexual function. With the exception of breastfeeding, peripartum expectations do not result in altered sexual functioning at 12 months postpartum. Spaich S, Link G, Alvarez SO, et al. Influence of Peripartum Expectations, Mode of Delivery, and Perineal Injury on Women's Postpartum Sexuality. J Sex Med 2020;17:1312-1325.

The Lack of Evidence for an Association between Cancer Biomarker Conversion Patterns and CTC-Status in Patients with Metastatic Breast Cancer.

Circulating tumor cell (CTC) detection is a prognostic factor in the metastatic breast cancer (MBC) setting. Discrepancies in primary (PT) and metastatic tumor (MT) genetic profiles are also of prognostic importance. Our study aimed to compare the CTC statuses and prognoses between those with subtype stable MBCs and MBCs with specific biomarker conversions. The study enrolled 261 MBC patients, treated at the National Center for Tumor Diseases, Heidelberg, Germany in a five-year period. All underwent PT and MT biopsies and subsequent CTC enumeration before the initiation of systemic therapy. ER and HER2 statuses of the PTs and MTs were determined and progression free survivals (PFSs) and overall survivals (OSs) were recorded. We compared CTC statuses, CTC counts, PFSs and OSs between subgroups of patients with different receptor change patterns. Patients who had tumors that converted to triple negative MTs had the shortest median OSs, while HER2 expression was not associated with a shorter median OS. No significant differences in PFSs and OSs have been demonstrated by Kaplan-Meier curve comparisons in any of the subgroup analyses. CTC counts were similar in all subgroups. CTCs were comparably less frequently detected in patients with a stable HER2 expression. Similar proportions of CTC positives were observed in all other subtype change pattern subgroups, barring the aforementioned HER2 stable subgroup. The detection of CTCs was of no appreciable prognostic value in different receptor change pattern subgroups in our cohort.

Single-center long-term results from the randomized phase-3 TARGIT-A trial comparing intraoperative and whole-breast radiation therapy for early breast cancer.

PURPOSE: Partial breast irradiation using intraoperative radiotherapy (IORT) after breast-conserving surgery could be sufficient for a selected group of breast cancer patients. We report the results of a cohort of patients from a single center treated as part of the randomized phase-3 TARGIT-A trial. METHODS: Patients (≥50 years) with cT1 cN0 cM0 and invasive ductal histology on biopsy were randomized between IORT with 20 Gy (arm-A) or postoperative whole-breast RT (WBRT) up to 56 Gy in 2 Gy fractions (arm-B). Postoperatively, patients in arm-A with multifocality, lymphovascular invasion, nodal invasion, extensive intraductal component, invasive lobular carcinoma, or resection margins <1 cm received additional postoperative WBRT. RESULTS: Between 2002 and 2012, 184 patients were randomized, of whom 90 in arm-A and 90 in arm-B were evaluated. Median follow-up was 8.5 years. The 5­year overall survival was 94.4% in arm-A and 93.3% in arm-B (p = 0.73). Two local recurrences were observed: one at 70.3 months in an arm-A patient who received IORT + WBRT and another at 4.5 months in an arm-B patient who refused all forms of adjuvant treatment, thus resulting in a 5-year local recurrence of 0% in arm-A and 1.1% in arm-B. The 5­year in-breast recurrence (outside of the index quadrant) was 0% in arm-A and 1.2% in arm-B. Salvage mastectomy was performed successfully in all patients with relapse. CONCLUSION: Long-term follow-up of this single-center cohort consolidates the earlier reports of low local recurrence rates after single-dose IORT. Our results are in line with non-inferiority of risk-adapted IORT for selected patients with early breast cancer.

Altered patient perceptions and preferences regarding male and female gynecologists: a comparison between 1997 and 2018.

PURPOSE: The purpose of this investigation was to explore changes in patient preference regarding gynecologist's gender. METHODS: Using a standardized questionnaire, distributed in 1997 and 2018, a total of 1000 women were interviewed about preferences in terms of their choice of gynecologist and perceptions regarding gender-dependency of gynecologist's qualifications, strengths and weaknesses. Data was correlated with sociodemographics and possible influencing factors. RESULTS: Based on their own experience, an increasing majority did not express a preference for their gynecologist's gender (58-71%). However, the minority that still favors one gender demonstrated a significant decrease in preference of male gynecologists (14-5%), while about a quarter still generally prefer treatment by female physicians. Sub-analyses of emotional and technical treatment aspects generally confirm these trends in that more of today's patients are indifferent to their gynecologist's sex and that the remaining minority shifts towards favoring female doctors. If asked to definitely choose between female and male physicians based solely on the aspect of trust a significant change can be noted (69-30%) in favor of female doctors in 2018 as opposed to 1997 when patients were split in this regard (52%/48%). Overall bad personal experience regarding gynecological treatment has significantly decreased (36% reduction). CONCLUSION: Over the last decades, patient preference and perception of the importance of their gynecologist's gender has changed. While an increasing majority attributes equal competence in emotional, professional and interpersonal aspects to both genders, the remaining proportion of patients demonstrates a significant shift towards favoring female doctors.

Patient preferences regarding intraoperative versus external beam radiotherapy for early breast cancer and the impact of socio-demographic factors.

PURPOSE: Patient comfort and preference have steadily gained attention in radio-oncologic treatment of breast cancer. Therefore, the purpose of this investigation was to further explore patient preferences in choosing between intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT). METHODS: We prospectively analysed data of 101 women, who were candidates for breast-conserving surgery with adjuvant radiotherapy. A two-part video was shown to patients: an educational section about EBRT/IORT, followed by a preference elicitation section focusing on additional accepted risk (AAR) of recurrence after either treatment. Furthermore, participants completed a questionnaire to identify factors that influence patient preference of radiation modality. RESULTS: The data demonstrate that 42.5% of patients would accept additional risk of recurrence for IORT versus 9% AAR for EBRT, while 48.5% of patients would not accept any additional risk, yet would choose IORT over EBRT if risks of recurrence were equivalent. When combining patient preferences and the results from the questionnaire, no single socio-economic/-demographic factor was found to significantly correlate with AAR of IORT. CONCLUSION: Our study confirms the existence of subgroups of breast cancer patients who would accept an additional risk of recurrence associated with choice of radiation modality to receive a single dose of IORT as adjuvant radiotherapy for breast cancer instead of EBRT over several weeks; yet our data fail to identify a single factor significantly associated with these patient preferences and, therefore, helpful for individualised decision-making processes.

[Induction of Labour In Growth Restricted and Small for Gestational Age Fetuses - A Historical Cohort Study]. / Ist die Geburtseinleitung bei intrauteriner Wachstumsrestriktion und small-for-gestational-age-Feten problematisch? Eine historische Kohortenstudie.

PURPOSE: Induction of labour for small-for-gestational-age (SGA) foetus or intrauterine growth restriction (IUGR) is common, but data are limited. The aim of this trial was therefore to compare labour induction for SGA/IUGR with cases with normal fetal growth beyond the 10th percentile. MATERIAL AND METHODS: This historical multicentre cohort study included singleton pregnancies at term. Labour induction for SGA/IUGR (IUGR group) was compared with cases of fetal growth beyond the 10th percentile (control group). Primary outcome measure was caesarean section rate. RESULTS: The caesarean section rate was not different between the 2 groups (27.0 vs. 26.2%, p=0.9154). In the IUGR group, abnormal CTG was more common (30.8 vs. 21.9%, p=0.0214), and fetal blood analyses were conducted more often (2.5 vs. 0.5%, p=0.0261). There were more postpartum transfers to the NICU in the IUGR group (40.0 vs. 12.8%, p<0.0001), too. CONCLUSION: Induction of labour for fetal growth restriction was not associated with an increased rate of caesarean section.

Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation.

BACKGROUND: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. METHODS: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. RESULTS: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. CONCLUSION: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.